This proposal contains specific features of the studies on the oncogenicity of Marek's disease virus (MDV). In specific aims I, II and III, we plan to study the detailed aspect of D-H region which is uniquely expanded in nonpathogenic strains of MDV and which may contain a possible tumor inducing gene of MDV. We will obtain more biological evidence that D-H region may be needed for tumor induction and/or transformation. This will be done by proposed studies such as co-transfection of nonpathogenic viral DNA with D-H fragment to recover pathogenic viral strain, transformation or immortalization of cells by D-H transfection, and determination of tumorgenicity in chicken for viruses with normal D-H and expanded D-H, plaque purified from a weakly oncogenic virus strain. MDV-induced lymphoblastic cell DNA will be tested for NIH 3T3 cell transformation to examine whether chicken cell DNA sequence may be present for inducing HIH 3T3 cell transformation. Structure and transcriptional patterns of D-H region will be studied. D-H gene products will be synthesized by mammalian vector or bacterial plasmid and characterized. Other unique structural features of MDV DNA will also be studied. Other viral genes actively transcribed in transformed cells and tumors will be identified. Finally, DNA of herpesvirus turkey (HVT), which is used as a vaccine for prevention of MD, will be physically mapped by restriction enzymes and colinearity of viral DNA between MDV and HVT will be determined. Cross-reactive antigens between MDV and HVT will be assigned to the maps of both virus by in vitro transplantation method. This study will be important for the future genetic study of MDV and HVT.